Ruthenium(III) dimethyl sulfoxide pyridinehydroxamic acid complexes as potential antimetastatic agents: synthesis, characterisation and in vitro pharmacological evaluation

摘要

Reaction of 3-pyridinehydroxamic acid and 4-pyridinehydroxamic acid (3-pyha and 4-pyha) with either [NBu4][RuCl4(dmso-S)2] or [(dmso)2H][RuCl4(dmso-S)2] (dmso is dimethyl sulfoxide) in acetone afforded three new ruthenium(III) dimethyl sulfoxide pyridinehydroxamic acid complexes: [NBu4][trans-RuCl4(dmso-S)(4-pyha)]·CH3COCH3 (1), [3-pyhaH][trans-RuCl4(dmso-S)(3-pyha)] (2) and [4-pyhaH][trans-RuCl4(dmso-S)(4-pyha)] (3). The solid-state structure of [NBu4][trans-RuCl4(dmso-S)(4-pyha)]·CH3COCH3 (1) was determined by X-ray crystallography. 2 and 3 were pharmacologically evaluated for their in vitro cytotoxicity, their ability to inhibit cell invasion and their gelatinase activity. 2 and 3 were devoid of cytotoxicity against the cell lines tested. 2 inhibited invasion of the highly invasive MDA-MB-231 cells to a much greater extent than 3. Contrary to expectations, neither 2 nor 3 had any inhibitory effect on matrix metalloproteinase (MMP) production and/or activity and in fact 3 was found to enhance the production and/or activity of both MMP-2 and MMP-9.